IMMUNOREGULATION AND IMMUNE RECOGNITION IN FILARIASIS AND NON-FILARIAL DISEASES

本项目的目的是阐明 调节丝虫病患者的体液和细胞反应 和其他疾病状态，并确定这些抗原负责 引发这些反应。 寄生虫抗原驱动的抗体产生的体外模型以及 寄生虫特异性的人T细胞和B细胞克隆已经被开发， 更详细地了解调节抗体产生的机制 （特别是IgG和IgE）在丝虫病、过敏性疾病和 正常的情况。 此外，HTLV-1转化的T细胞克隆携带T细胞 已经制备了活化抗原和Fc γ受体， 分离参与T细胞调节该同种型（IgE）的因子 在寄生虫病中表达上调。 这些T细胞作为 以及携带Fc ε受体（FcER）的B细胞系， 用于分离、纯化和产生针对最近 使这种受体的基因得以分子克隆。 免疫系统识别的抗原的定性分析 已经进行了B和T细胞水平的检测， 已构建盘尾丝虫种特异性抗原。 来源于以下的人单克隆抗体识别的抗原 还鉴定了EBV转化的患者B细胞。 FPLC分析 丝虫寄生虫的抗原成分已经确定并帮助 以部分纯化某些似乎调节免疫的分子， 在细胞和体液水平的反应人丝虫病。 免疫印迹法检测血吸虫、脂肪肝和肝硬化患者血清中丝虫特异性IgE和IgG 丝虫病和盘尾丝虫病的抗原模式 不同临床表现的患者组之间的识别不同 丝虫病的临床表现和具有类似表现的人群 但他们接触寄生虫的时间长短不同

The purpose of this project is to delineate the mechanisms involved in regulating the humoral and cellular responses in patients with filariasis and other disease states and to determine those antigens responsible for inducing these responses. In vitro models of parasite-antigen driven antibody production as well as parasite-specific human T cell and B cell clones have been devloped to understand in more detail those mechanisms regulating antibody production (Particularly IgG and IgE) in filariasis, allergic diseases and in the normal situation. Further, HTLV-1 transformed T cell clones bearing T cell activation antigens and Fc epsilon receptors have been made in order to isolate fators involved in the T cell regulation of this isotype (IgE) which appears to be up-regulated in parasitic diseases. These T cells as well as a B cell line bearing the Fc epsilion receptor (FcER) have been used to isolate, purify, and raise antibody to the FcER which has recently enabled the gene for this receptor to be cloned molecularly. Qualitative analysis of the antigens recognized by the immune system at both a B and T cell level has been performed and T cell lines recognizing an Onchocerca volvulus species specific antigen has been constructed. Antigens recognized by human monoclonal antibodies derived from EBV-transformed patient B cells have also been identified. FPLC analysis of the antigenic components of filarial parasites has identified and helped to partially purify certain molecules which appear to regulate the immune response at both the cellular and humoral level human filariasis. Immunoblot analysis of filaria-specific IgE and IgG in loiasis, lyphatic filariasis and onchocerciasis have indicated patterns of antigen recognition which differ among groups of patients with different clinical manifestations of filariasis and among those with similar manifestations but who have been exposed to the parasite for different lengths of time.